ICMI 2015

F.82 Expression of the TGFβ-Activating Integrin αvβ8 on Dendritic cells is Important for Regulation of Human T Cell Responses

Friday, July 17, 2015
Grand Hall and Gallery, Ground Floor & 1st Floor (Maritim Hotel)
Thomas Fenton , University of Manchester, Manchester, United Kingdom
Markus Lehtinen , DuPont Nutrition and Health, Kantvik, Finland
Mark Travis , University of Manchester, Manchester, United Kingdom
A balance of TH17 cells and regulatory T cells (Tregs) is required to maintain immune homeostasis in the intestine. Activation of the cytokine TGFβ, which is secreted as an inactive complex, plays a crucial role in the induction of both Treg and TH17 cells. However, while murine studies have highlighted important pathways that regulate TGFβ activity in the intestine, little is currently known about the mechanisms of TGFβ activation in humans.

Here we have shown that the TGFβ-activating integrin αvβ8, which we have previously found to play an important role in murine intestinal immune homeostasis, is preferentially expressed on human CD1c+ intestinal dendritic cells (DC). Interestingly, expression on these cells is increased during pathological inflammation. We find that expression of integrin αvβ8 is upregulated on human DC after LPS stimulation, suggesting the enhanced expression of αvβ8 during inflammation could be driven by an infiltrating microbiota. Importantly, we have also shown that TGFβ activation by αvβ8 on human DC promotes CD25+CD127- Foxp3+ Treg induction ex vivo. Together, our data suggest that integrin αvβ8-mediated TGFβ activation by DC may play a role in the regulation of T cell responses in the human intestine, and that this pathway may be perturbed during intestinal inflammation.